In this competing renewal application of a Merit award, Dr. DiMaio describes a series of experiments to investigate various aspects of the interaction between the bovine papillomavirus type 1 (BPV-1) E5 protein and the cellular PDGF beta receptor. Based upon studies performed during the prior funding period, Dr. DiMaio has proposed a model to explain how the E5 protein forms a dimer and binds to the PDGF beta receptor, and how this interaction results in receptor activation that contributes to cellular transformation. Six aims are proposed: 1) to determine the molecular basis for the ability of E5 to discriminate between the PDGF beta receptor and = the closely related PDGF alpha receptor. 2) To identify the helical interface that mediates E5 dimerization, 3) to test the model that each E5 monomer contributes to the productive binding of E5 dimer to PDGF beta, 4) to characterize the signaling that occurs as a consequence of E5's activation of the PDGF beta receptor, 5) to test the hypothesis that certain mutants of E5 can interfere with PDGF beta signaling and 6) to identify novel peptide sequences that can contribute to the multimerization and activation of PDGF beta receptor